tbuckley/cabot-search huggingface dataset:
A retrospective study evaluating the efficacy of pembrolizumab for metastatic or locally recurrent head and neck cancer: A real-world experience.
Authors: Jonathan P. Pirruccello, Muhammad Zubair Afzal, John P Palmer, Maura Dore, Keisuke Shirai
Journal: Journal of Clinical Oncology (2023)

e18018 Background: Metastatic and locally recurrent head and neck cancer is an unfortunate occurrence and is associated with a historically poor prognosis. The KEYNOTE 048 trial reported an overall response rate (ORR) of 17% in this patient population after treatment with pembrolizumab. The purpose of our study is to evaluate the real-world outcomes in patients with metastatic or recurrent head and neck cancers treated with pembrolizumab or pembrolizumab containing regimens at our NCI designated comprehensive cancer center. Methods: We reviewed the medical records of 39 patients with advanced head and neck cancers treated with pembrolizumab or pembrolizumab containing regimens between 9/1/2017 and 12/31/2021. Patients with a diagnosis of cutaneous squamous cell carcinoma in the head and neck region and nasopharyngeal cancers were excluded. Results: Thirty-seven patients were included in the final analysis with a median age of 67. The median time to last follow-up was 12 months with a median time on therapy of 3.2 months. The most common location was oropharynx (87%), and 59% of the study population had documented CPS scores greater than 1. Approximately 60% of patients had distant metastatic disease at the time of initiation of pembrolizumab including one patient with symptomatic brain metastases prior to initiation of therapy. The most common site of metastatic disease was the lungs (51%). The ORR was 11.7%, while the median OS and median PFS were 10 and 2.9 months, respectively. Three patients experienced a complete response (CR), including one patient with a lasting, durable response of 50.9 months. The six-month and one-year PFS were 100% in those who responded or had stable disease (five patients). Ten patients (27%) required hospitalization due to treatment related adverse effects. Conclusions: The role of pembrolizumab in the setting of advanced head and neck cancer is well-established based on findings from large clinical trials. We report an ORR of 11.7% and median PFS of 2.9 months in patients treated with pembrolizumab containing regimens. Although the findings of our small retrospective study suggest a lower response rate than previously reported, the progression free survival in responders at six and twelve months was 100%. Identification of potential responders to immunotherapy has been an active area of research and our study suggests that a subset of patients with metastatic and/or locally recurrent head and neck cancer may experience long and durable responses to pembrolizumab containing regimens. [Table: see text]
The impact of ImmunoPrecision in small bowel adenocarcinoma.
Authors: Vi Kien Chiu, Jessica Belmonte, Diaa Osman, Jun Gong, Andrew Eugene Hendifar, Arsen Osipov, Emil Lou, Sharvina Ziyeh, Karen Zaghiyan, Nicholas Nissen
Journal: Journal of Clinical Oncology (2023)

e16333 Background: Although approaches to treating adenoCA of the small bowel (SBA) are extrapolated from those of the colon, SBA has distinct pathogenesis, clinical presentation and poorer prognosis. We examine the impact of SBA treatment by ImmunoPrecision, which combines Immunotherapy and Precision genomic targeting. Methods: SBA pts were identified retrospectively from Cedars-Sinai electronic health record (2000 – 2022) on an IRB-approved protocol. Microsatellite status and genomic testing were done in CLIA-certified, CAP-accredited labs. Pt characteristics, pathology, in-depth clinical history and genomics were summarized with descriptive statistics. Endpoint of median OS was estimated by Kaplan-Meier and calculated from pre-treatment imaging to last event. Treatment groups were compared using log-rank test. Results: Between Jan 2003 – Dec 2022, 137 stage 1 – 4 SBA pts (93 duodenal; 44 jejunal/ileal) were identified. Median age was 67 (range 22 – 95). Microsatellite status and genomic testing data were done or known for 72 pts (53%). In 35 pts who had metastases at initial presentation, 15 pts had NGS genomics, which identified actionable targets: 20% Her2 amp/mut , 13% FGFR1 amp/mut , 7% ALK fusion , 7% KRAS G12C, and 7% ATM R35*. 40% of 10 metastatic pts tested for microsatellite status were MSI/TMB-High, and only 1 pt received immunotherapy. In pts with metastases, median OS was 9.5 mo in duodenal adenoCA (51 pts) vs 13.0 mo in jejunal/ileum adenoCA (23 pts) (p = 0.46). There was a non-significant improvement in median OS to 20.5 mo in metastatic duodenal adenoCA pts who received targeted inhibition of actionable genomics or had MSI/TMB-High status (p = .51). Conclusions: Our real-world cohort of metastatic duodenal adenoCA shows a trend toward improved median OS from ImmunoPrecision targeting of frequent MSI/TMB-High status and actionable genomics. ImmunoPrecision clinical trial investigation is warranted in this rare SBA population. [Table: see text]
Clinical features of long-term survivors with advanced high-grade serous ovarian cancer.
Authors: Maria-Pilar Barretina-Ginesta, Anna Carbó Bagué, Elisabet Bujons, Arola Fortian, Claudia Fina, Marta Pardo, Cristina Melendez-Muñoz, Laura Cardenas, Anna Taltavull, Josep Sabaté, Esther Darder, Lidia Feliubadalo, Jordi Barretina, Joan Brunet
Journal: Journal of Clinical Oncology (2023)

e17575 Background: Most patients diagnosed with high-grade serous ovarian cancer (HGSOC) at advanced stages (FIGO III&amp;IV) have limited survival. However, approximately 30% of patients survive more than 5 years, some of them without relapse. A better understanding of these patients may uncover novel factors contributing to their long survival beyond those known to be related to HGSOC prognosis (age, stage and residual disease after surgery). This descriptive study aims to analyze the clinical characteristics of these exceptional survivors and describe them in contrast to patients with worse survival in a cohort of patients diagnosed before the introduction of PARP inhibitors as first-line maintenance therapy. Methods: A descriptive analysis of patients newly diagnosed with advanced HGSOC at our University Hospital between 2009 and 2018 was conducted. We report clinical characteristics of long-term survivors (LTS), defined as patients alive after 5 years(y) from the date of diagnosis and characteristics of patients who survived less than two years from the date of diagnosis, classified as short- term survivors (STS). Results: Among 195 patients with advanced HGSOC 42 (21,5%) survived less than 2y and 48 (24,6%) more than 5y, 18 of them (37,5%) without relapse. The Median age was 61.1y for LTS and 64.8 for STS. In the LTS group, 77.1% of patients were stage III, and 22.9% were stage IV. In the STS group, the distribution of patients with stage III and IV was 42.9% and 57.1%, respectively. A higher proportion of LTS underwent surgery n=44 (91,7%), most of them as interval debulking surgery (59.1%). Almost half of STS did not undergo surgery (45,2%), being interval debulking surgery the most frequent systematic approach when surgery was performed (73.9%). Only 9,1% of LTS who underwent surgery had residual disease compared to 27,3% of STS. Harboring mutations in the BRCA1/2 genes is a favorable prognostic factor also associated with chemotherapy sensitivity, in our serires 23% of LTS were BRCA1&amp;2 mutation carriers (11 patients (23%) patients with germline BRCA mutations being 7patients(15%) BRCA1mut and 4patients(8%) BRCA2mut with 4patients(8%) of patients not analyzed). Conclusions: In our cohort, stage III and cytoreduction surgery were more frequent among LTS. Classical clinical characteristics are not enough to identify advanced HGSOC LTS. More investigation on their molecular profile might help to to identify exceptional LTS in order to elucidate better management approaches and new treatments for patients with worse prognosis.
Extracranial palliative radiotherapy for metastatic renal cell carcinoma.
Authors: Young Suk Kwon, Eric Hsu, Maggie Stein, Alana Christie, Aurelie Garant, Andrew Zhuang Wang, Daniel X. Yang, Allen Yen, Mihailo Miljanic, Kevin Dale Courtney, Hans J. Hammers, Tian Zhang, Waddah Arafat, Qian Qin, Suzanne Cole, James Brugarolas, Robert D. Timmerman, Raquibul Hannan
Journal: Journal of Clinical Oncology (2023)

e24156 Background: Radiation therapy (RT) is routinely used for the palliation of metastatic renal cell carcinoma (mRCC) symptoms despite a paucity of literature on RT’s efficacy. Since RCC is considered radioresistant to conventionally fractionated RT, we retrospectively evaluated factors influencing effective symptom palliation with RT for mRCC. Methods: A retrospective review of patients with mRCC between 2011 and 2022 at a high-volume academic radiation center was performed to identify patients with symptomatic extracranial metastatic sites managed with RT. Radiation therapy techniques included three-dimensional conformal RT, intensity-modulated RT, and stereotactic body RT. Symptomatic indications for RT were categorized as pain, neurologic (weakness and numbness), respiratory (hemoptysis and cough), gastrointestinal/genitourinary (GI/GU) bleeding, or multiple. Symptom relief was evaluated from chart reviews at subsequent on-treatment visits or follow-up encounters. Time to symptom alleviation (days) was measured from the RT start date. Descriptive analyses were performed. Results: Of 243 patients included in the study cohort, there were 617 irradiated sites. 560 out of 617 (91.0%) patients were treated for pain, and the other symptoms included neurologic (6.8%), respiratory (3.9%), and GI/GU bleeding (1.5%). The most common RT regimen was 20Gy in 5 fractions (122 lesions; 19.8%) followed by 30Gy in 10 fractions (35 lesions; 5.7%). Symptom relief was observed in 84.9% (95%CI 81.4, 88.1) of patients for pain, 90.8% (95%CI 78.2, 97.6) for neurologic, and 69.9% (95%CI 49.3, 88.0) for respiratory symptoms. The overall proportion of symptom relief was 103/131 (79%) for 20 Gy in 5 fractions versus 27/38 (71%) for 30 Gy in 10 fractions (chi-square P = 0.3). Conclusions: RT is effective for symptom palliation of mRCC. Further studies are required to fully delineate the impact of dose-fractionation and RT modality. [Table: see text]
Efficacy of checkpoint inhibitors in hospitalized patients with cancer.
Authors: Yusra B. Medik, Vinit Singh, Marina Alsabaawy, Gabriella Gerbino, Farhan Khalid, Priyaranjan Kata, Mariela Divanna, Nashwa Yosry, Trishala Meghal, Vinod Nookala
Journal: Journal of Clinical Oncology (2023)

e14687 Background: Pembrolizumab is approved by FDA in 2014 to treat metastatic melanoma. Use of immune check point inhibitors (ICI) has been expanding in multiple cancer types including non-small cell lung cancer since then. In this mini case series, we will evaluate the benefits and risks of immunotherapy in hospitalized patients. Use of immunotherapy agents in inpatient unit has been associated with poor clinical outcome and higher cost. Byrne et. al have recently shown that more than 45% of hospitalized patients receiving PD1 or PD-L1 antibodies have either died or discharged to hospice care. A large retrospective chart review in Dana Farber Cancer Institute reveals 86% mortality rate in hospitalized immunotherapy recipients within the study period. Understanding the safety and advantages of using immune checkpoint inhibitors in inpatient unit has a pivotal role in decreasing the healthcare associated costs and setting the appropriate goals of care with patients and families. Methods: This is a retrospective observational cohort study conducted by review of electronic health records in last 5 years (from January 1 st 2017- January 1 st 2022) in Rutgers Health Community Medical Center and Monmouth Medical Center. Adult patients admitted to inpatient unit who received Pembrolizumab, Atezolizumab, or Nivolumab were included. Results: A total of 61 patients has received ICI therapy while in hospital with 57% males and 42% female. All patients had solid tumors, with most common malignancy being lung cancer (55%) followed by colon cancer (14%). Most common ICI given was pembrolizumab (62%) followed by atezolizumab (18%) and Nivolumab (16%). 26% of patients that were treated died in the hospital, 35% were transferred to another care facility and 29% were discharged home. No immune-related adverse events were reported. Age groups, cancer types were comparable with regard to discharge status. Conclusions: Poor mortality and survival outcome from this case series should prompt clinicians to consider benefit and risks of ICI therapy when prescribed to patients who were hospitalized for non-oncological acute conditions.
Durvalumab + tremelimumab in biologically selected advanced/metastatic solid tumors.
Authors: Christelle De La Fouchardiere, Carlos A. Gomez-Roca, Aymeric De Montfort, Antoine Italiano, Marine Gilabert, Olivier Tredan, Iphig nie Korakis, Isabelle Laure Ray-Coquard, Pauline Rochefort, Armelle Dufresne, Sophie Cousin, Christophe Le Tourneau, Benoit You, Francois Bertucci, Philippe Alexandre Cassier, Valéry Attignon, Romaine Mayet, Gwenaelle Garin, David Pérol, Jean-Yves Blay
Journal: Journal of Clinical Oncology (2023)

2604 Background: Tremelimumab (T) in combination with Durvalumab (D) is approved by the FDA for the treatment of unresectable hepatocellular carcinoma and metastatic non–small cell lung cancer. We prospectively examined its clinical activity in a cohort of biologically-selected advanced/metastatic solid tumors from the MOST Plus clinical trial (NCT NCT02029001). Methods: Adult patients (pts) previously treated by at least one prior line but immunotherapy-naive were eligible if their tumor harbored TMB-H (&gt;10mut/Mb) and/or MSI/dMMR (by PCR and IHC tests), and/or PD1/PD-L1/CTLA4 amplification and/or POLD1 or POLE mutation. T was administered for up to 4 cycles (75mg, IV, Q4W) and D (1500mg, IV, Q4W) until disease progression, unacceptable toxicity or patient/investigator decision. Tumor response was assessed as per RECIST 1.1 and adverse events reported according to NCI-CTCAE v4.03. Results: 70 patients were enrolled (24 male, median age: 65 years [33-88], MSI n=56, TMB-H n=10, PDL1 and PDL2 ampl. n=1, POLE mut. n=1, MSH6 mut. n=1, MSH2 mut. n=1). The median number of prior lines of systemic therapy was 1 (range: 0-4). Main tumor types were colorectal (44%), endometrial (19%), and stomach (7%) carcinomas. As of October 2022, overall response (ORR) rate was 52.8% (21.4% CR, 31.4% PR). With a median follow-up of 37 months, median PFS and OS were 8.4 months [95% CI: 4.4- 22.1] and 37.2 months [95% CI: 10.4-NE], respectively. Median duration response of response was not reached. Overall, 24.3% of patients experienced at least one serious treatment-related (TR) adverse event. Two TR-deaths were reported (haemophagocytic lymphohistiocytosis and nephritis). ORR, median PFS and OS are reported. Conclusions: T+D is a highly efficient combination in biologically selected tumors leading to a high complete response rate. Enrolment is still ongoing, to further evaluate the utility of a maintenance treatment, i.e the optimal treatment duration. Clinical trial information: NCT02029001 . [Table: see text]
Use of tumor mutational burden as a predictive marker of response to immuno-oncology agents: Initial experience at an academic center in Venezuela.
Authors: Guillermo Borga, Santiago Sucre, Oscar Sucre, Liliam Vivas, Hector Salazar, Carlos Eduardo Sucre
Journal: Journal of Clinical Oncology (2023)

e14613 Background: Tumor Genetic Profiling (TGP) is steadily becoming the mainstay of clinical practice, namely, the Tumor Mutational Burden (TMB) is believed to be a predictor of efficacy to treatment with Immune Checkpoint Inhibitors (ICI). Recent studies have demonstrated that a high-TMB score (TMB-H) is associated with higher response rates. In Venezuela, the evidence of mutational frequencies obtained by TGP is limited, herein we present our experience at a large educational institution. Methods: In this retrospective cohort, we included 80 subjects with different types of solid tumors to whom TGP was performed to determine TMB values, as well as other associated mutations, between January 2020 and December 2022. In a subgroup of subjects in which ICI therapy was formally indicated (n=21) we used the Objective Response Rate (ORR) as a primary endpoint, recorded as the percentage of patients who had a complete response (CR) or partial response (PR), based on the RECIST v1.1 criteria. Treatment options included Ipilimumab, Atezolizumab, Pembrolizumab and Nivolumab, as either monotherapy or in combination according to the corresponding NCCN guidelines. A TMB-H score was defined as greater than 10 mutations per megabase. Results: A TMB-H was found in 11 samples, subjects with lung cancer accounted for the majority of this finding (n=6). The most frequently reported mutations were BRCA 1-2 (n=9), KRAS (n=9), and EGFR (n=4). In the subgroup treated with ICI, the ORR of the group with TMB-H was 71.42%, while in those with low TMB it was 35.71%. The differences in response rates, with a 95% CI, yielded a p=0.122; which corresponds to a statistically non-significant outcome. Conclusions: This study constitutes the first country-level documentation of what is becoming a standardized practice, and contributes to the growing evidence regarding the use of TMB-H as a marker to predict response to treatment. Our small cohort demonstrated a high ORR to ICI when a TMB-H score is present, albeit to a non-statistically significant degree. We will continue to follow-up these patients, as well as to include newly sequenced samples for TGP, to give greater statistical power to these findings.
Incidence of venous thromboembolism with immune checkpoint inhibitors in a community setting: A single-center retrospective study.
Authors: Madhan Srinivasan Kumar, Vidit Majmundar, Sumukh Arun Kumar, Chidambaram Ramasamy, Kala Seetharaman
Journal: Journal of Clinical Oncology (2023)

e14681 Background: Immune activation and inflammation caused by immune checkpoint inhibitors (ICIs) are critical pathobiological drivers for venous thromboembolism (VTE). There is a paucity of data about VTE risk in cancer patients receiving ICI. We aimed to describe the incidence of VTE in cancer patients receiving ICI in a community setting. Methods: We conducted a single center, retrospective cohort study at Saint Vincent Hospital. The study cohort was created using our center's pharmacy database of patients who received any of the five ICIs (ipilimumab, nivolumab, pembrolizumab, atezolizumab, or durvalumab) between Jan 2017 and Dec 2022. VTE events including deep venous thrombosis, splanchnic vein thrombosis, and pulmonary embolism, were identified by chart review. We used a self-controlled risk-interval design, with "control period" and "at-risk period" being 6 months before and after the initiation of ICI treatment respectively. VTE events were also analyzed for subgroups: Single-agent ICI therapy (IA), Dual ICI therapy (IB), and ICI + chemotherapy (IC). Descriptive statistics and cox regression were used for statistical analysis. Results: Study population included 170 patients, with 75, 14, and 81 patients in subgroups IA, IB, and IC respectively. The mean age of the patients was 69.51 ± 10.05 years with a majority being males (62.4%). The most common cancer observed was non-small cell lung cancer (43.5%) followed by small cell lung cancer (6.9%), and malignant melanoma (5.7%). Pembrolizumab (55.3%) was the most common ICI used and nivolumab + ipilimumab (7.64%) was the most common dual ICI used. We noted a 1.25-fold higher incidence of VTE post-ICI use (Incidence rate ratio [IRR]: 11.76 per 100 person-year) compared to pre-ICI use (IRR: 9.41 per 100 person-year) at 6 months. On subgroup analysis, Group IB had the highest risk for VTE at 6 months (IRR: 28.57 per 100 person-year), followed by group IC and IA (IRR: 14.12 and 8.0 per 100 person-year respectively). IRR decreased to 6.62 per 100 person-year at 12-month interval indicating increased VTE risk in the first 6 months of ICI exposure. Type of ICI, adjuvant chemotherapy or type of cancer was not able to predict VTE risk on multivariate analysis. Conclusions: ICI treatment was associated with an increased incidence of VTE in our study cohort with the highest risk among patients on dual ICI followed by ICI + chemotherapy and ICI monotherapy. Future prospective studies are needed to identify risk factors and biomarkers to improve risk stratification and risk-adapted thromboprophylaxis.[Table: see text]
Effect of machine learning-based integration develops M2 macrophage-activation genes signature on outcomes in nasopharyngeal carcinoma.
Authors: Zongwei Huang, Ying Li, Xiaochuan Chen, Sufang Qiu
Journal: Journal of Clinical Oncology (2023)

e14581 Background: The M2 macrophages are independent prognostic factors in nasopharyngeal carcinoma (NPC). Nevertheless, the clinical significance of M2 macrophages remains largely unexplored. Methods: We applied public single-cell sequencing data (GSE150825) to reconstruct a pseudotime trajectory of macrophage polarization in NPC and analyzed the gene expression patterns along the trajectory. GeneSwitches was used to identify the order of the critical regulatory gene during M2 macrophage activation. A novel computational framework was constructed to screen the M2 macrophage-activation genes (MAGens) for developing MAGens signature by integratively analyzing the transcriptomes data of single-cell, published dataset (GSE102349, N=88) and Fujian NPC dataset (N=188) using 10 machine learning algorithms (101 combinations). Results: Combining single-cell transcriptomics with GeneSwitches analyse, we identified SPP1 as the top switching gene and the order at which the switch takes place for the state of M2 macrophage activation. At the bulk transcriptome level, we found that the high expression of SPP1 had poor prognosis and more infiltration of M2 macrophages. Immunohistochemistry was used to validate the association between the critical regulatory gene expression and M2 macrophages. Then we analyzed the differential expressed genes (DEGs) upregulated by M2 macrophages at the single-cell transcript level. And the NPC transcriptome data was used to identify SPP1-related genes and prognostic genes. Based on the share genes of M2 macrophage DEGs，SPP1-related genes and prognostic genes, we established a five-gene MAGens signature which exhibited highly diagnostic accuracy in predicting progression-free survival in patients with NPC. Conclusions: We explored the role of SPP1 in NPC progression, M2 macrophage polarization and established an MAGens signature related prognostic model for NPC. MAGens signature could serve as a robust and promising tool to improve clinical outcomes for individual NPC patients.